Sulfonyloxy esters of



United States Patent 2,734,06 SULFONYLOXY ESTERS 0F fi-AIVIINOALCOHOLS.

Theodore A. Geissman, Los Angeles, Calif.,, assignor to Smith, Kline 8a. FrenchLaboratories, Philadelphia, Pa., a corporation of Pennsylvania No Drawing. Application September 22', 1950, Serial No. 186,317

9 Claims.v (Cl. 260-456) This invention relates to new chemical compounds, more particularly to sulfonic acid esters of B-aminoalcohols.

The compounds of this invention possess physiological activity; more particularly they will be useful as sympatholytic agents.

The compounds of this invention, from the broad stand-point, have the following structure:

N-CHaGHz-OSOzRHOSOrR in which:

R is selected from the group consisting of aralkyl, the alkyl portion of which contains not more than 3 carbon atoms; and aralkyl, the alkyl portion of which contains not more than 3 carbon atoms, and substituted in the aryl nucleus with a substituent selected from the group consisting of methyl, methoxy and halogen.

R is selected from the group consisting of lower alkyl, benzyl and benzyl substituted in the phenyl nucleus with a substituent selected from the group consisting of methyl, methoxy and halogen.

R is selected from the group consisting of lower alkyl; phenyl; phenyl substituted with a substituent selected from the group consisting of methyl, methoxy and halogen; and naphthyl.

More specifically, the compounds according to this invention will have the following structure:

R is selected from the group consisting of phenyl alkyl, the alkyl portion of which contains not more than 3 carbon atoms; phenyl alkyl, the alkyl portion of which contains not more than 3 carbon atoms and substituted in mice . 2' from the group consisting of methyl, rnethoxy, chlorine and bromine; and fl-naphthyl.

The compounds according to this invention will be prepared, preferably, byreacting the silver salts of sulf'onic the phenyl nucleus with a substituent selected from the acid with a halogen derivative,v prepared by treating a fl-amino alcohol with thionyl halides to form the. corresponding sulfonic acid ester in the form of' the salt of, the sulfonic acid. This method of preparation is illustrated by the reaction shown below, the values for R, R and R being as given above and X representing a halogen atom:

The compounds. according to this invention and procertur f r the r Preparati n w l be rther l rated. y the following specific examples:

EXAMPLE 1 Dibenzyl-p-benzenesulfonyloxyethylamine benzenesulfon N-OEzCHrOS0r@.HOSOa- A mixture of 18g, of dibenzyl-fi-chlorethylamine hy-. drochloride and g. of silver benzenesulfonate was refluxed overnight in 200 ml. of dry acetone. The hot solution was filtered through celite and the filter cake was washed several successive times with small portions of acetone. The resulting clear solution was concentrated d ry her d unt l. urb d y w s n ticed- The pr u s g t d in rys ll form upon cool n and, was recrystallized from acetone by the. wldi im. 1 dry ether to yield a product melting at 119-1205.

EXAMPLE 2 Dibenzyl-pp-toluenesulfonyloxy -ethylamine p-toluenesulfonate 4 20 g. of dibenzyl-fi-chloroethylamine hydrochloride by the addition of ether. Reprecipitation and recrystaland 60 g. of silver p-toluenesulfonate in 200 m1. of dry lization of the product from acetone and ether provided acetone was treated in a manner identical with that dea product melting at 103.5-105. scribed in Example 1 above. The ester product upon The tit-naphthylmethyl-ethyl-[3-iodoethylarnine hydrorecrystallization melted at 144-146". 5 iodide used as a starting material above, was prepared EXAMPLE 3 from the corresponding ,B-chloro compound. A solution of 5 gm. of a-naphthylmethyl-ethyl-p-chloroethylamine ly -B-0 p f y y) y hydrochloride and 7.6 gm. of sodium iodide in 150 m1. fi' p y f of acetone was refluxed for 16.5 hours. The solid was filtered and was found to contain most of the iodo com- Qg pound. The acetone solution was concentrated to 50 ml., N-omom-oso .Hoso cooled, and the crystals that deposited were filtered. The combined solid fractions were recrystallized from absolute ethanol to yield light yellow crystals melting at 166.5- 167 (d). 2 g. of dibenzyl-fl-chloroethylamine hydrochloride and EXAMPLE 6 5 g. of silver fi-naphthalenesulfonate were refluxed in 50 ml. of dry methylethyl ketone, and the product isolated as described in Example 1 above. The fl-naphthylsulfonic salt of the ester so obtained melted at 125-l27 C. after two recrystallizations from acetone. Analysis of this \NCHQCHQOSO5CH3.HOSO9CH3 Dibenzyl-fl-methylsulfonyloxyethylamine methylsulfonate product disclosed the compound to contain one molecule OH of acetone of crystallization. 2

EXAMPLE 4 Dibenzyl-[B- (p-bromobenzenesulfonyloxy -ethylamine p-bromobenzenesulfonate g. of silver p-bromobenzenesulfonate and 10 g. of This compound will be prepared using a procedure dibenzyl-B-chloroethylamine hydrochloride was covered 35 ldenilcal W1th that descllbed 1n f p W1 th the 200 ml of anh dmus acetone and refluxed for 48 ceptlon that sllver methylsulfonate Wlll be used in place of W y silver benzenesulfonate. hours with constant mechanical stirring. The mixture i while still hot was then filtered through a small Buchner EXAMPLE 7 funnel and the residue was washed with acetone. Upon 4o Dibenzyl-fl-(n-plopylsulfonyloxy)-ethylamine n-propylthe addition of dry ether to the concentrated filtrate there sulfonate appeared a turbidity. Cooling separated an oil which, @0112 upon redissolving in dry, hot acetone, was caused to crystallize by the addition of further dry ether. The white crystalline product melted at 107110 C.

= EXAMPLES V Ethyl-a-naph thylm-ethyl-13-( p-toluenesulfonyloxy) -ethylamine p-toluenesulfonate A miFKtuIC of eof P Y y y -fl- This compound will be prepared using a procedure ethylamme hydroiodide and 18 g. of silver p-toluenesulidentical with that deScn-bed in Example 1, with the g i :2 :3 zf gg fi igi zg f g i i E 32; ception that silver n-propylsulfonate will be used in place iodide by filtration the" product was precipitated as an oil f l benzenesulfonate- EXAMPLE 8 Phenylethyl-benzyl-fi- (p-methoxybenzenesulfonyloxy) ethylamine p-methoxybenzensulfonate am er This compound will be prepared according to the pro cedure described in Example. 1:, with, the exception. that dibenzyl-fi-chlorethylamine will be replaced. by di-(mchlorobenzyD-B- chlorethylamine hydrochloride, and silver benzenesulfonate will be replaced by silver p-bromobenzenesulfonate EXAMPLE 12 Phenylisopropyl-benzyl fl (p-toluenesulfonyloxyy ethylamine, p-toluenesulfonate silver benzenesulfonate be replaced by silver p-methoxybenzenesulfonate.

EXAMPLE 9 Di- (p-tolylmethyl) -fl-benzenesulfonyloxyethylamine benzenesulfonate This compound will be prepared using. a procedure identical with that described in Example 1, with the exception that di-(p-tolylmethyl)-13-chloroethylarnine hy- ,HOSO:

This compound will be prepared according to the procedure described. in Example 1 with the exception that dibenzyl-[B-chloroethylamine will be replaced by phenyl- 30- isopropyl-benzyl-fl-chloroethylamine hydrochloride, and

silver benzenesul'fonate will be replaced by silver p-toluenesulfonate.

EXAMPLE 13 Benzyl- (-3,4-dimethoxyphehylisopropyl) -}3-b,enzene- CHSO drochloride will be used in place of dibenzyl- -chloroethylamine.

EXAMPLE l0 Di-(p-methoxybenzyl 1-5-(p-chlorobenzenesulfanyloxy)- ethylamine p-chlorobenzenesulfonate sulfonyloxyethylami'ne benzenesulfonate This compound will beprepared according to the procedure described in Example 1, with the exception that This compound will be prepared according to the procedure described in Example 1, with the exception that dibenzyl-B-chloroethylarnine will be replaced by di-(pmethoxybenzyl-)-;8-chloroethylamine hydrochloride, and silver benzenesulfonate will be replaced by silver p-chlorobenzenesulfonate.

EXAMPLE 11 Di-(n-chlorobenzyl)48-(p-bromobenzenesulfonyloxy)- ethyhrmine, p-bromobenzenesulfonare dibenzyl-B-chloroethylamine will be replaced by benzyl- (3A:dimethoxyphenylisopropyl)-fi-chloroethylamine hy- 60 drochloridie.

7 EXAMPLE 14 Isobutyl-phenylisopropyl-fi-(p'-naphthalenesulfonyloxy)- ethylamine fi'maphthale nesulfonate -om-o 11-0113 .HOSO fi (CHshCH-C'Hz-N-CHzCHz-OSO This compound will be prepared according to the procedure described in Example 1, with the exception that dibenzyl-fi-chloroethylamine will be replaced by isobutylphenylisopropyl-fi-chloroethylamine hydrochloride, and silver benzenesulfonate will be replaced by silver S-naphthalenesulfonate.

EXAMPLE 15 n-Heptyl-benzyl-fi-benzenesulfonyloxyethylamine benzenesulfonate @e /NCH2CHzOSOz-.HOSO2 GEE-(C1190 OHaCH-z This compound will be prepared according to the procedure described in Example 1, with the exception that dibenzyl-fl-chloroethylamine will be replaced by ethylm-chlorobenzyl-B-chloroethylamine hydrochloride.

EXAMPLE l7 Isopropyl-benzyl-fi-ethylsulfonyloxyethylamine ethylsulfonate NC H20 H2-O S -0 2H5.H0 50 2-0 2115 8 What is claimed is: 1. Sulfonyloxy esters of fi-aminoalcohols having the structure:

in which R is selected from the group consisting of aralkyl, the alkyl portion of which contains not more than 3 carbon atoms; aralkyl having not more than 3 carbon atoms in the alkyl portion and substituted in the aryl nucleus with a methyl group; aralkyl having not more than 3 carbon atoms in the alkyl portion and substituted in the aryl nucleus with a methoxy group; aralkyl having not more than 3 carbon atoms in the alkyl portion and substituted in the aryl nucleus with a halogen atom; R is selected from the group consisting of lower alkyl, benzyl, benzyl substituted in the phenyl nucleus with a methyl group; benzyl substituted in the phenyl nucleus with a methoxy group; benzyl substituted in the phenyl nucleus with a halogen atom; and R is selected from the group consisting of lower alkyl, naphthyl, phenyl, methyl substituted phenyl, methoxy substituted phenyl and halogen substituted phenyl.

2. The compound having the following formula:

3. The compound having the following formula:

CHzC

4. The compound having the following formula:

5. The compound having the following formula:

zenesulfonate will be replaced by silver ethylsulfonate.

OHIO

. l v Y omo-Q-em-pn-orn 6. The compound having the following formula:

7. The compound having the following structure:

8. Sulfonyloxy esters of B-aminoalcohols having the structure:

NOHsCHr-OSOzRIIOSOaR in which R is aralkyl having a benzene ring which is 15 linked to the nitrogen through at least one and no more than two aliphatic carbon atoms and having not in excess of three aliphatic carbon atoms; R" is selected from the group consisting of lower alkyl and benzyl; and R is in which R is aralkyl having a benzene ring which is linked to the nitrogen through at least one and no more than two aliphatic carbon atoms and having not in excess of three aliphatic carbon atoms; R" is selected from the group consisting of lower alkyl and benzyl; and in which X is a halogen; is mixed with a compound having the formula:

AgOSOzR in which R is selected from the group consisting of lower alkyl, phenyl and tolyl; in the presence of a non-hyselected from the group consisting of lower alkyl, phenyl 2 droxylic solvent and tolyl.

9. The process for obtaining a sulfonic acid ester of 2- dialkylamino-ethanols in which a compound of the class consisting of a free base and its hydrohalide addition,

salts, the free base having the formula: 2

NCHgOHg-X References Cited in the file of this patent UNITED STATES PATENTS 2,504,977 Gump Apr. 25, 1950 

1. SULFONYLOXY ESTERS OF B-AMINOALCOHOLS HAVING THE STRUCTURE: 